After leaving Cambridge United, the seventeen-year-old was offered a trial with West Ham and impressed Academy director Tony Carr enough to be offered a first year scholarship.

Collison continued his development under Carr and his staff at Little Heath before being made reserve team captain at the start of the 2007–08 season.[7] That summer, the teenager also featured in pre-season friendlies against Hornchurch and Milton Keynes Dons. He was named in the West Ham first team squad for the first time in November 2007 for the home game against Bolton Wanderers,[8] and made his first team debut on 1 January 2008, when he came on as a substitute for the injured Freddie Ljungberg in the Premier League away loss to Arsenal.[9][10] On 11 April away at Bolton Wanderers, he was handed his first league start in place of the injured Mark Noble.

A dream summer was completed as Collison signed a new five-year contract with the Hammers shortly before joining the first-team squad on the pre-season tour of North America. There, he appeared as a second-half substitute in the 3–1 win over MLS side Columbus Crew and 3–2 defeat by the MLS All-Stars. The 2008–09 season began with Collison in Alex Dyer's reserve team, and a loan move to League One promotion-chasers Peterborough had been lined up. However, an impressive substitute appearance in the 2–0 Premier League loss at Manchester United on 29 October coupled by injury problems in the midfield convinced manager Gianfranco Zola that Collison would be better served by remaining at Chadwell Heath and training with the first-team squad.

Collison repaid Zola's faith with more solid performances. He scored his first goal for West Ham, an 18-yard strike, on 8 November against Everton in a 3–1 defeat at Upton Park after coming on as a substitute for the injured Matthew Upson to make his home debut.[7][11] The goal was nominated for the Goal of the Season awards on the West Ham fansite Knees Up Mother Brown. His good form earned him praise from Zola,[12] who rewarded the twenty-year-old with a new five-year contract extension in December before the winter break.[13] On Boxing Day, he scored the equaliser at Portsmouth and had a hand in the next two goals in a 4–1 rout.[14] He scored his third goal of the season, the only goal of the match against Manchester City on 1 March 2009.[15] Although he mostly played in centre midfield during his days in the reserves, he eventually established himself as first-choice on the left side of Zola's midfield diamond.[16]

In the away win at Wigan Athletic three days later, Collison dislocated his kneecap while attempting to chest down a long ball and was ruled out for six weeks.[17] He returned to the team in May two months later, coming on as a late substitute in the 1–0 win away at Stoke City.[18] On 24 May, he finished the season on a high, by assisting Junior Stanislas to score the winner, in a 2–1 win over Middlesbrough.[19]

Collison was chosen as Young Hammer of the Year by Tony Carr.[20] On 23 August 2009 Collison played 89 minutes of the 2009–10 Premier League fixture against Tottenham Hotspur, before learning that his father had been killed in a motorcycle accident, while travelling to the game.[21]

Collison celebrating scoring a goal in May 2012 in a 3–0 win against Cardiff City.

Two days later, he started a League Cup tie against Millwall that went into extra time and ended 3–1 to West Ham. His teammates all wore black armbands to show their support and fans applauded him when the team entered the stadium. The match also featured a number of pitch invasions and violent clashes between fans outside the ground. After full-time, Collison left the pitch in tears visibly upset.[22] During the post-match interview, manager Gianfranco Zola complimented Collison's character in light of his father's death.[23] After missing most of September's games due to the recurrence of the knee injury suffered at Wigan last season, Collison returned to training in October and made his comeback in the 9 October, behind-closed-doors friendly against French side Valenciennes, scoring a goal himself,[24] and then marked his return to league action by making the starting eleven in the away loss at Stoke City eight days later.[25] He scored his first goals of the season in consecutive matches, against Hull City and Burnley. Having not played since Wales' 1–0 defeat to Sweden on 3 March 2010, on 7 May 2010, it was announced that he would be out for around nine months after undergoing knee surgery having never fully recovered from the cartilage damage he suffered in the 2008–09 season.[26]

After fourteen months out through injury, Collison made his first-team return on 7 May 2011 against Blackburn Rovers in a 1–1 draw at Upton Park.[27] On 7 August 2011, he came on for Mark Noble on 74 minutes against Cardiff City at Upton Park in the opening Championship league fixture in a 1–0 defeat. Four days later Collison committed his future to the football club by signing a new long-term deal with West Ham.[28] On 15 October he scored his first goal of the season in the 4–0 win over Blackpool at Upton Park.[29] After just over a month out of the first team line up, Collison returned in the final away game of the season against Leicester City with West Ham needing to win to take automatic promotion into the final day of the season. With the score at 1–1, Collison hit a 25-yard shot that beat Kasper Schmeichel giving West Ham the points needed.[30] Finishing in 3rd place with 86 points West Ham entered the Football League Championship play-offs. On 3 May 2012, Collison scored twice in a 2–0 win against Cardiff City in the first leg of the play-offs semi-final and again in the second leg to make the aggregate scoreline 5-0. [31] Collison was released by West Ham at the end of the 2013-14 season.[32] He had played 121 games in all competitions for West Ham scoring 14 goals.[33]

On 1 October 2013 Collison signed a one month's loan with AFC Bournemouth.[34] He made his debut the same day in a 2-1 away defeat to Leeds United. [35] At the end of October 2013, after playing four games for Bournemouth, Collison returned to West Ham United.[36]

In September 2014, Collison joined Ipswich Town on a short term contract until the end of December 2014.[39] After struggling with injury during his time with Ipswich, by December 2014 he had not played for the side and manager, Mick McCarthy, confirmed that Collison's contract would not be renewed.[40]

Collison is eligible to play for Wales through his grandfather who was born in Bedwellty, Monmouthshire[41] and is related to John Gwilliam, a former captain of the Wales rugby union team.[42] Though born in England, Collison chose to play for Wales due to Welsh ancestry on his mother's side.[43] His then-West Ham teammate and former Wales captain Craig Bellamy had alerted Wales youth coach Brian Flynn about Collison's eligibility. After observing the nineteen-year-old, Flynn named him in the squad to face the Bosnia-Herzegovina Under-21's in a UEFA European U-21 Championship qualifier.

Collison made his senior debut for Wales in an away friendly win against Iceland on 29 May 2008.[51] Bellamy praised the young midfielder saying, "I've seen him every afternoon at West Ham and he does extra training. If you want to give this career a good go then you get the rewards and that seems to be how Jack is looking at it."[52] After the death of Collison's father, national team coach John Toshack gave him the choice whether to make himself available for selection. Having played in West Ham's last two games, he declared himself available for the qualifier against Russia. This match would confirm Collison as a full Wales international, as his previous six caps all came in friendlies.[53] He did not play, however, as he had to attend his father's funeral, which took place on the day of the match. With the recurrence of the knee injury, he was ruled out of Wales' qualifying campaign that ultimately ended with a fourth place finish in the group.

With Collison back to full fitness, Toshack named him in the 23-man squad for the 14 November friendly against Scotland.[54] Flynn also named him amongst 11 other senior internationals in the preliminary squad to face the Bosnia-Herzegovina Under-21's in a qualifier on 18 November.[55][56] Collison ended up having to withdraw after picking up a knock during the weekend match against Everton.[57] In November Collison was in the final nomination for the Welsh Young Player of the Year award along with Simon Church and Aaron Ramsey.[58]

On 6 September 2011, Collison made his competitive debut in the Euro 2012 qualifier against England and put to rest further speculation about his future at the international level.[59][60]